Histopathological findings in a COVID-19 patient affected by ischemic gangrenous cholecystitis.

BACKGROUND: Since its first documentation, a novel coronavirus (SARS-CoV-2) infection has emerged worldwide, with the consequent declaration of a pandemic disease (COVID-19). Severe forms of acute respiratory failure can develop. In addition, SARS-CoV-2 may affect organs other than the lung, such as the liver, with frequent onset of late cholestasis. We here report the histological findings of a COVID-19 patient, affected by a tardive complication of acute ischemic and gangrenous cholecystitis with a perforated and relaxed gallbladder needing urgent surgery. CASE PRESENTATION: A 59-year-old Caucasian male, affected by acute respiratory failure secondary to SARS-CoV-2 infection was admitted to our intensive care unit (ICU). Due to the severity of the disease, invasive mechanical ventilation was instituted and SARS-CoV-2 treatment (azithromycin 250 mg once-daily and hydroxychloroquine 200 mg trice-daily) started. Enoxaparin 8000 IU twice-daily was also administered subcutaneously. At day 8 of ICU admission, the clinical condition improved and patient was extubated. At day 32, patient revealed abdominal pain without signs of peritonism at examination, with increased inflammatory and cholestasis indexes at blood tests. At a first abdominal CT scan, perihepatic effusion and a relaxed gallbladder with dense content were detected. The surgeon decided to wait and see the evolution of clinical conditions. The day after, conditions further worsened and a laparotomic cholecystectomy was performed. A relaxed and perforated ischemic gangrenous gallbladder, with a local tissue inflammation and perihepatic fluid, was intraoperatively met. The gallbladder and a sample of omentum, adherent to the gallbladder, were also sent for histological examination. Hematoxylin-eosin-stained slides display inflammatory infiltration and endoluminal obliteration of vessels, with wall breakthrough, hemorrhagic infarction, and nerve hypertrophy of the gallbladder. The mucosa of the gallbladder appears also atrophic. Omentum vessels also appear largely thrombosed. Immunohistochemistry demonstrates an endothelial overexpression of medium-size vessels (anti-CD31), while not in micro-vessels, with a remarkable activity of macrophages (anti-CD68) and T helper lymphocytes (anti-CD4) against gallbladder vessels. All these findings define a histological diagnosis of vasculitis of the gallbladder. CONCLUSIONS: Ischemic gangrenous cholecystitis can be a tardive complication of COVID-19, and it is characterized by a dysregulated host inflammatory response and thrombosis of medium-size vessels.

Extended resection for xanthogranulomatous cholecystitis mimicking gallbladder carcinoma: Cases and review of diagnostic approach.

Xanthogranulomatous cholecystitis is a rare variant of chronic cholecystitis, which can involve adjacent organs including liver, colon and duodenum mimicking gallbladder cancer. Preoperative and intraoperative differentiation of xanthogranulomatous cholecystitis from gallbladder cancer is often difficult and the final diagnosis is made on histopathology of the resected specimen. We hereby report four cases of xanthogranulomatous chol ec ystitis w hich were misdiagnosed as cases of advanced gallbladder cancer based on presentation and radiological findings and underwent radical resections but the final histopathology was a diagnostic surprise. Xanthogranulomatous cholecystitis is still a diagnostic challenge as no single modality has been helpful to diagnose this entity till date. Radical resection seems justified in patients who present with the features mimicking gallbladder cancer.

New Avenues in the Regulation of Gallbladder Motility-Implications for the Use of Glucagon-Like Peptide-Derived Drugs.

CONTEXT: Several cases of cholelithiasis and cholecystitis have been reported in patients treated with glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) and GLP-2 receptor agonists (GLP-2RAs), respectively. Thus, the effects of GLP-1 and GLP-2 on gallbladder motility have been investigated. We have provided an overview of the mechanisms regulating gallbladder motility and highlight novel findings on the effects of bile acids and glucagon-like peptides on gallbladder motility. EVIDENCE ACQUISITION: The articles included in the present review were identified using electronic literature searches. The search results were narrowed to data reporting the effects of bile acids and GLPs on gallbladder motility. EVIDENCE SYNTHESIS: Bile acids negate the effect of postprandial cholecystokinin-mediated gallbladder contraction. Two bile acid receptors seem to be involved in this feedback mechanism, the transmembrane Takeda G protein-coupled receptor 5 (TGR5) and the nuclear farnesoid X receptor. Furthermore, activation of TGR5 in enteroendocrine L cells leads to release of GLP-1 and, possibly, GLP-2. Recent findings have pointed to the existence of a bile acid-TGR5-L cell-GLP-2 axis that serves to terminate meal-induced gallbladder contraction and thereby initiate gallbladder refilling. GLP-2 might play a dominant role in this axis by directly relaxing the gallbladder. Moreover, recent findings have suggested GLP-1RA treatment prolongs the refilling phase of the gallbladder. CONCLUSIONS: GLP-2 receptor activation in rodents acutely increases the volume of the gallbladder, which might explain the risk of gallbladder diseases associated with GLP-2RA treatment observed in humans. GLP-1RA-induced prolongation of human gallbladder refilling may explain the gallbladder events observed in GLP-1RA clinical trials.

Volume kinetics of Ringer's lactate solution in acute inflammatory disease.

BACKGROUND: Little is known about the turnover of crystalloid fluids infused in patients with acute systemic inflammation. We hypothesised that systemic inflammation would be associated with altered distribution and elimination of Ringer's lactate solution (volume kinetics). METHODS: Ringer's lactate solution (15 ml kg-1) was infused intravenously over 35 min in patients undergoing cholecystectomy (n=20) or appendectomy (n=20) starting before induction of general anaesthesia. Blood samples and urine were collected over the following 2 h. Plasma concentrations of inflammatory (tumour necrosis factor-α, interleukin-10, and C-reactive protein) and endothelial damage (syndecan-1) biomarkers were quantified by enzyme-linked immunosorbent assay. The volume kinetics was studied using mixed-effect modelling. RESULTS: Ongoing surgery (duration: 30-45 min) increased the rate constant for fluid transfer from the plasma to the extravascular space (k12; from 32 to 57×10-3 min-1; P<0.001), and decreased the elimination rate constant (k10; from 5.3 to 0.6×10-3 min-1; P<0.001). A lower mean arterial pressure was associated with reduced elimination, independent of conscious/anaesthetised state. The redistribution of fluid back to the plasma occurred more slowly in the group with appendicitis (P<0.02), in whom higher plasma concentrations of C-reactive protein were measured [median: 38.1 (range 1.8-143.6) vs 1.3 (0.1-159.0) µg ml-1; P<0.001]. However, no biomarkers for inflammation or endothelial damage were significantly associated covariates in the kinetic model. CONCLUSIONS: No association was found between the volume kinetics of Ringer's lactate solution and the degree of inflammation as indicated by established biomarkers in patients with cholecystitis or appendicitis. However, the rate of elimination was greatly retarded by general anaesthesia in both groups. CLINICAL TRIAL REGISTRATION: ChiCTR-IOR-15006063.

Exercising the hepatobiliary-gut axis. The impact of physical activity performance.

BACKGROUND: Physical inactivity puts the populations at risk of several health problems, while regular physical activity brings beneficial effects on cardiovascular disease, mortality and other health outcomes, including obesity, glycaemic control and insulin resistance. The hepatobiliary tract is greatly involved in several metabolic aspects which include digestion and absorption of nutrients in concert with intestinal motility, bile acid secretion and flow across the enterohepatic circulation and intestinal microbiota. Several metabolic abnormalities, including nonalcoholic fatty liver as well as cholesterol cholelithiasis, represent two conditions explained by changes of the aforementioned pathways. MATERIALS AND METHODS: This review defines different training modalities and discusses the effects of physical activity in two metabolic disorders, that is nonalcoholic fatty liver disease (NAFLD) and cholelithiasis. Emphasis is given to pathogenic mechanisms involving intestinal bile acids, microbiota and inflammatory status. RESULTS: A full definition of physical activity includes the knowledge of aerobic and endurance exercise, metabolic equivalent tasks, duration, frequency and intensity, beneficial and harmful effects. Physical activity influences the hepatobiliary-gut axis at different levels and brings benefits to fat distribution, liver fat and gallbladder disease while interacting with bile acids as signalling molecules, intestinal microbiota and inflammatory changes in the body. CONCLUSIONS: Several beneficial effects of physical activity are anticipated on metabolic disorders linking liver steatosis, gallstone disease, gut motility, enterohepatic circulation of signalling bile acids in relation to intestinal microbiota and inflammatory changes.

[Non-functioning gallbladder as a risk factor for bile ducts injury during laparoscopic cholecystectomy]. / Nefunktsioniruiushchii zhelchnyi puzyr' kak faktor riska travm zhelchnykh protokov pri laparoskopicheskoi kholetsistéktomii.

AIM: To analyze the effect of gallbladder's morpho-functional changes as a risk factor for injury of extrahepatic bile ducts during cholecystectomy. MATERIAL AND METHODS: Laparoscopic cholecystectomy was performed in 20 564 patients. There were 147 64 (71.8%) patients with chronic gallbladder inflammation and 5800 (28.2%) - with acute process. It was performed a retrospective analysis of the incidence and causes of intraoperative trauma of extrahepatic bile ducts and bile outflow. Two groups of comparison were distinguished: acute calculous cholecystitis and chronic inflammation. RESULTS: There were 93 (0.04%) complications followed by bile outflow (55 (0.94%) in the 1st group and 38 (0.25%) in the 2nd group). Marginal injury of the ducts was interoperatively detected in 5 patients of group 1 and 3 patients of 2 groups. In postoperative period it was found in 6 patients of the 1st group due to electric trauma of common bile duct. Complete transection of common bile duct occurred in 10 (8.8%) cases, while chronic calculous cholecystitis was observed in 8 of them. At the same time, in 6 patients these were surgical interventions in scleroatrophic gallbladder. As a results, we determined the forms of non-functioning gallbladder with morphofunctional changes which promote trauma of extrahepatic bile ducts. CONCLUSION: Long-term non-functioning gallbladder leads to cicatricial and adhesive processes in its wall and surrounding tissues that significantly complicates cholecystectomy and increases the risk of bile ducts trauma. Scleroatrophic gallbladder is the most dangerous which occurs in 4.1% of patients with chronic calculous cholecystitis. Further trials are advisable to develop optimal therapeutic and diagnostic tactics for various forms of long-term non-functioning gallbladder.

Gallbladder Dysfunction: Cholecystitis, Choledocholithiasis, Cholangitis, and Biliary Dyskinesia.

The prevalence of gallstones is 10% to 15% in adults. Individuals with acute cholecystitis present with right upper quadrant pain, fever, and leukocytosis. Management includes supportive care and cholecystectomy. The prevalence of choledocholithiasis is 10% to 20%, and serious complications include cholangitis and gallstone pancreatitis. The goal of management in individuals with choledocholithiasis consists of clearing common bile duct stones. Acute ascending cholangitis is a life-threatening condition involving acute inflammation and infection of the common bile duct. Treatment includes intravenous fluids, analgesia, intravenous antibiotics, and biliary drainage and decompression. Biliary dyskinesia includes motility disorders resulting in biliary colic in the absence of gallstones.

[Chronorehabilitation of the patients suffering from chronic cholecystitis with concomitant gallbladder dysfunction and opisthorchiasis]. / Khronoreabilitatsiia bol'nykh khronicheskim kholetsistitom s disfunktsiei zhelchnogo puzyria i opistorkhozom.

The importance of the development of the effective rehabilitative measures for the patients suffering from chronic cholecystitis with concomitant gallbladder dysfunction and opisthorchiasis is beyond question. The adequate methods for the rehabilitation of the patients after an intensive de-worming remain to be developed. It is known that de-worming is not infrequently followed by the immediate amplification of the manifestations of the stagnation of bile in the gallbladder that become even more pronounced than before the de-worming procedure. With the purpose of improving the effectiveness of the spa and health resort-based rehabilitation and prevention of the complications, it is recommended to make use of the modern therapeutic physical factors to be prescribed taking into consideration the characteristics of the biological rhythms in the functional activity of the biliary system in the individual patients. The most effective rehabilitation methods for the treatment of the pathology in question include the application of the therapeutic physical factors known to produce the beneficial effect on the functional state of the biliary system and exert the normalizing influence on the structure of the biological rhythms of the functional activity of various organs and systems. We used a range of approaches for the treatment of 123 patients with chronic cholecystitis and concomitant gallbladder dysfunction plus opisthorchiasis including extremely high-frequency electromagnetic irradiation (EHF therapy) in the combination with the oral intake of the choleretic herbal remedies followed by the transverse galvanization of the epigastric region with due regard for the phase of the rhythm of the functional activity of the gallbladder. The results of such treatment gave evidence of the positive dynamics of all the studied indicators of the functional activity of the biliary system and the organism as a whole which suggests the highest therapeutic effect (87.9%) of the proposed treatment that was maintained during 6 to 12 months.

Juxtarenal Mycotic Aneurysm as a Complication of Acute Exacerbation of Chronic Cholecystitis Treated by Resection and Replacement by a Fresh Allograft.

We present a case of a female patient with infectious (mycotic) juxtarenal abdominal aneurysm with atypical symptoms beginning as acute exacerbation of chronic cholecystitis. Apart from common antibiotic treatment, the patient successfully underwent resection of the diseased segment and replacement by a fresh allograft in order to reduce the risk of infection of the graft, but with the need of subsequent life-long immunosuppressive therapy. Perioperative monitoring of the spinal cord by near infrared spectroscopy was used to identify possible spinal ischemia. The choice of the fresh allograft was based on our experience supported by review of the literature.

[Biliary infections : cholecystitis and cholangitis]. / Infections des voies biliaires : cholécystite et cholangite.

Biliary infections are a common cause of emergency department visit, usually of benign evolution but that can sometimes progress rapidly to a life-threatening emergency.The mainstay of treatment of acute cholecystitis is urgent laparoscopic cholecystectomy, performed in 72 hours.Antibiotic treatment is often sufficient for the initial treatment of mild cholangitis. A percutaneous or endoscopic biliary drainage must be done urgently in case of severe presentations or if the patient doesn't respond to conservative treatment. The definitive treatment of the cause of cholangitis, will be performed in a second time.

Les infections de la vésicule et des voies biliaires sont un motif fréquent de consultation aux urgences. Leur évolution est le plus souvent bénigne, mais elles peuvent parfois devenir rapidement une urgence vitale.Le pilier du traitement de la cholécystite aiguë est la cholécystectomie laparoscopique en urgence, réalisée dans un délai inférieur à 72 heures.L'antibiothérapie est souvent suffisante pour le traitement initial de Ia cholangite simple. Un drainage biliaire percutané ou endoscopique doit être effectué en urgence pour une cholangite sévère ou en cas de non-réponse au traitement conservateur. Le traitement définitif de la cause de la cholangite sera pratiqué dans un deuxième temps.

ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH HYPOTHYROIDISM AND CONCOMITANT CHRONIC CHOLECYSTITIS.

Activity of endothelial dysfunction markers in patients with hypothyroidism and concomitant chronic cholecystitis was investigated. In patients with hypothyroidism and chronic cholecystitis a increased lactate dehydrogenase and alkaline phosphatase activity was observed, accompanied by the manifestation of cholestasis. In this patients increased vascular endothelium growth factor plasma level and endotheliocytes number was detected, attested the accelerated severity of endothelium dysfunction. Inverse correlation between the vascular endothelium growth factor plasma concentration, desquamated endotheliocytes number in peripheral blood and bilirubin level was detected, that points to the protective role of bilirubin in the prevention of the endothelium dysfunction development.

[Optimization of cholecystectomy method in patients with professional diseases of respiratory organs].

Results of cholecystectomy performance were analyzed in 99 patients with a biliary calculous disease, the course of which have become complicated by cholecystitis occurrence, in 49 of them professional diseases of respiratory organs, including silicosis, antracosis, were registered. Estimating results of laparoscopic and open cholecystectomy, we have established, that carboperitoneum in laparoscopic cholecystectomy impacts negatively the course of early postoperative period, what manifests with hemodynamic and respiratory disorders. The level of fibronectin and endotelin--1 in the blood plasm directly depends on the respiratory disorders severity and may be applied as a test for respiratory dysfunction. The method of cholecystectomy in patients, suffering professional diseases of respiratory organs, must be selected, depending on severity of functional disorders of respiratory organs.